In this project we assessed the potential effectiveness of three vaginal microbicides myeloperoxidase delivered with lactobacilli (MPO+LB), a 0.25% chlorhexidine gluconate formulation (CHG), and octylglycerol, a lipid derived from human breast milk. For each microbicidal compound, we assessed baseline vaginal flora, pH, cytology, and colposcopy and collected cervical swabs for chlamydia detection by culture and LCR. We then added a gel containing MPO+LB, 0.25% CHG, octylglycerol, or appropriate placebo gel, while positive control animals were inoculated with chlamydia only. The gel containing MPO+LB appeared to protect 3 of 4 monkeys from chlamydial infection when assessed by culture and LCR. Vaginal flora was not adversely affected in this group of animals, and the exogenous lactobacilli were transiently detected at increased levels in some of the pretreated monkeys. The 0.25%CHG gel protected all 5 pretreated animals, while the chlamydia control animals tested pos iti ve repeatedly after inoculation. Changes in vaginal flora were minimal in all monkeys. 0.25% CHG did not adversely effect vaginal colonization by lactobacilli. Colposcopic observations revealed a brief induction of cervical and vaginal erythema in animals from both groups. Finally, the octylglycerol lipid was shown to protect 5 of 6 monkeys from chlamydial infection when assessed by culture alone, but only 1 of 6 when cervical swabs were assessed by LCR. It is possible that chlamydial infection was suppressed, delayed or rendered non-infectious by the lipid formulation. Monkeys pretreated with the lipid, as well as those given the placebo gel, developed marked changes in their vaginal flora. It is possible that this lipid, when delivered in an improved gel formulation, will prove to be more protective against infection, and less disruptive to the cervicovaginal environment. FUNDING NIH grants RR00166 and AI39061. Patton, D.L., Cosgrove Sweeney, Y.T., McKay, T.L., Clark, A.M., Rabe, L.K., and Hillier, S.L. 0.25% Chlorhexidine gluconate gel A protective topical microbicide. Sex. Trans. Dis. 25:421-424, 1998. Patton, D.L., Cosgrove Sweeney, Y.T., McKay, T.L., Clark, A.M., Rabe, L.K., and Hillier, S.L. Effects of a single application of 0.25% chlorhexidine gluconate on vaginal flora and chlamydial infection in a monkey model. Fertil. Steril. 69:584, 1998. Patton, D.L., Cosgrove Sweeney, Y.T., Clark, A.M., Rabe, L.K., Klebanoff, S.J., and Hillier, S.L. Effects of a myeloperoxidase plus lactobacillus gel on vaginal flora and chlamydial infection in a monkey model. Abstr. 13 Mtg. Int. Soc. for STD Res., Denver, Co., July 11-14, 1999. Patton, D.L., Isaacs, C.E., Cosgrove Sweeney, Y.T., Clark, A.M., Rabe, L.K., and Hillier, S.L. Effects of a gel containing the lipid octylglycerol on vaginal flora and chlamydial infection in a monkey model. Abstr. 13 Mtg. Int. Soc. for STD Res., Denver, Co., July 11-14, 1999.